Sugar-Responsive Enzyme–Polyphenol ‘Tooth Nanoarmor’ for Long-Lasting Caries Prevention via Glucose Depletion and Biofilm Suppression

High sugar intake in modern dietary patterns heightens the risk of dental caries, yet current preventives neither address dietary sugars nor effectively inhibit cariogenic biofilms. Herein, we introduce a fully biomass-derived enzyme-polyphenol 'tooth nanoarmor' that self-assembles from glucose oxidase (GOx) and ellagic acid, a natural phenolic molecule found in pomegranate peels and tree bark. Noncovalent interactions mediate the self-assembly, yielding a porous supramolecular phenolic framework, with nanochannels exhibiting remarkable bioadhesion and biostability. Adhering to tooth enamel, the 'tooth nanoarmor' continuously depletes glucose and generates bactericidal H₂O₂. The 'tooth nanoarmor' reduces bacterial viability by 59% and exopolysaccharide accumulation by 83% <i>in vitro</i>. It also exhibits a long-lasting preventive effect manifested by a 94% reduction in Keyes score and a 47% increase in dentin mineral density <i>in vivo</i>. Our findings highlight an effective biohybrid 'tooth nanoarmor' based on the natural self-assembly of proteins and polyphenols for long-lasting prevention of dental caries.